Our data suggest that Tfh cells facilitate immune homeostasis by increasing the number of regulatory B cells and the production of IL-10 via the stimulation of IL-21 in SLE patients. All together, we define a novel role of Tfh cells in immune regulatory actions to promote production of the immunosuppressive cytokine IL-10, which extends the existing recognization that Tfh cells merely induce humoral responses and augment autoimmunity. Furthermore, IL-21 may serve as a potential upstream promoter for Breg cell differentiation and IL-10 production in SLE. These findings suggest that particular emphasis should be given to the regulatory function of Tfh cells and IL-21 in the treatment of SLE. Activating mutations in the Wnt and Ras signaling pathways are common in many epithelial cancers. Colorectal cancer, for example, usually starts with mutations in APC, a negative regulator of the Wnt signaling pathway followed, in,50% of CRC patients, by the oncogenic activation of K-Ras, an event that correlates with the onset of malignancy. This process can be reproduced in mouse models for CRC, where the conditional deletion of APC in the intestinal epithelium imposes a stem/progenitor-like phenotype, leading to massive crypt hyperproliferation and formation of benign MK-1775 abmole tumors known as adenomas. In turn, expression of K-Ras gain of function alleles in Apc mutant tumor cells induces the development of large, aggressive adenocarcinomas. However, whereas this genetic events leading to CRC have been well established, the precise genetic programs that these alterations impose, which role play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. It has been shown that the removal of APC specifically in the intestinal stem cells, but not in their progeny, leads to the formation of lesions that progress to adenomas in less than three weeks, suggesting that ISCs may represent the cell of origin of CRC. Mammalian ISCs are located at the base of the intestinal crypts, where they self-renew and generate a transient amplifying population. Finally arrest and differentiate towards enterocytes, enteroendocrine cells or goblet cells. Interestingly, there are many relevant similarities between mammalian and Drosophila intestines. The adult Drosophila midgut epithelium is also maintained by a population of ISCs that regenerate the stem cell pool or become quiescent progenitor cells, which ultimately differentiate towards enterocytes or enteroendocrine cells . The Wg/Wnt signaling pathway is required for both mammalian and fly intestinal stem cell homeostasis, and its constitutive activation in Drosophila through mutations in the APC homologues, Apc and Apc2, results in ISC hyperproliferation and midgut hyperplasia. Moreover, EGFR/Ras signaling pathway activity also promotes ISC division and is therefore required for ISC proliferation. Drosophila has been widely used to recapitulate key aspects of human cancer. Here, we generated clones that combined the loss of Apc with the expression of the oncogenic form of Ras, RasV12.